Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

356 R. W. Baker et al.Our primary focus is the relative response within diagnostic subgroups, especiallypsychotic versus non-psychotic, mixed versus manic, and rapid versus nonrapidcycling. When available, we report the group-by-treatment interaction,because a significant interaction would signal the potential usefulness of diagnosticcategorization to treatment selection. Most data are from mania studies. In orderto maintain consistent presentation across studies, we focus on improvement inthe primary mania rating scale; response rates; and relative results for diagnosticsubgroups. Further, as older antipsychotic agents are constrained in use for bipolardisorder by neurological and depressogenic side-effects, also reviewed are reportsof: study completion rates; impact of treatment on depression ratings; and extrapyramidaladverse events. In the interest of comparison across studies, we generallyconvert raw change to percentage change. For example, percent improvementin mania is calculated by dividing mean within-treatment group improvement bythe mean baseline mania rating score for that treatment group. P-values are notrevised with the conversion to percentage change, but are those reported for meanchange and interaction comparisons in the primary studies.ClozapineClozapine was the first of the atypical antipsychotic agents, with clinical trials inschizophrenia starting over three decades ago. Nevertheless, there are no blindedstudies of its use in bipolar disorder. Small, open trials are encouraging, includinguse adjunctive to other mood stabilizers for up to 1 year in a mixed group ofschizoaffective and bipolar patients (Suppes et al., 1999). A number of openreports (total n ¼ 42) on its efficacy for treatment–refractory mania (Calabreseet al., 1996; Green et al., 2000) have been reported. Controlled double-blindstudies in this subgroup would be welcome.RisperidoneTwo available double-blind trials of risperidone in patients with bipolar disorderexplored its usefulness as an adjunct to mood stabilizers for treating acute mania.One of these studies was positive. Sachs and collaborators (2002ab) reported adouble-blind 3-week study in patients with acute mania or mixed episodes beingtreated with divalproex or lithium, who were randomly assigned to adjunctivetreatment with risperidone 1–6 mg/day (n ¼ 52), haloperidol 2–12 mg/day(n ¼ 53), or placebo (n ¼ 51). Improvement from baseline to endpoint inYoung Mania Rating Scale (YMRS) was superior among patients receiving risperidone(51%) or haloperidol (49%) compared to placebo (29%). Though groupby-treatmentinteraction analysis is not reported, the mania rating mean changeresults suggest consistent therapeutic effects across psychotic and non-psychoticsubgroups for both haloperidol and risperidone as adjunctive treatment to mood